This grant will be under the administrative cognizance of the Department of Radiology within the School of Medicine. The department is professionally supported by the School of Medicine staff and the central university Grant and Contract Services organization. The PI, KA Krohn, and the co-PI, JF Eary, meet weekly with the project and core directors to review the progress of the research and to insure effective use of core resources by scheduling imaging studies. In addition, the administrative core will include data analysis and statistics. The data analysis and modeling group provides mathematical analysis of the kinetics of radiopharmaceutical biodistribution as both a research and a service component. In particular, we will extend mixture analysis to each of the projects over the next five years and apply novel heterogeneity analysis to the characterization of tumors using PET imaging. In order to increase the level of biostatistical involvement in protocol design and hypothesis testing, we have two small sub-contracts that are essential to the quality and overall productivity of our research program. The clinical utility of image-based information needs to be tested in terms of what additional information the PET-derived measurements contribute to the prediction of patient outcome at the treatment planning stage. Each of our hypotheses describes an observational study with imaging data, assays of relevant biomarkers, and measures of patient response/survival. At preset the imaging data is not used to influence patient's treatment, however, our goal is to identify imaging procedures where a clinically important improvement in predictive accuracy, beyond that attained with existing clinical and diagnostic methods, can be achieved. Because the improved prediction will have clear therapeutic implications and our results will pave the way for these hypotheses to be tested in future cooperative clinical trials, the consultants in biostatistics play a critical role in focusing protocols and directing data analysis in anticipation of cooperative prospective trials.